February 25, 2020
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Researchers identify factors linked to impaired hematopoietic recovery after CAR T-cell therapy

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Krishna R. Juluri, MD, PhD
Krishna R. Juluri

ORLANDO — Pre-lymphodepletion platelet count, disease type, in vivo chimeric antigen receptor T-cell expansion and grade of cytokine release syndrome each appeared associated with impaired hematopoietic recovery following CD19-directed CAR T-cell therapy, according to results of a retrospective study presented at TCT | Transplantation & Cellular Therapy Meetings.

These findings suggest prevention of cytokine release syndrome may improve hematopoietic recovery after CD19 CAR T-cell therapy, researchers noted.

“We tried to look at factors that are involved in mediating delayed hematopoietic recovery,” Krishna R. Juluri, MD, PhD, hematology/oncology fellow in the clinical research division at Fred Hutchinson Cancer Research Center, told Healio. “Something very interesting we found is that lymphodepletion did not correlate with delayed recovery. I was surprised to see that.”

CD19-targeted CAR T-cell therapy has been effective for some patients with relapsed or refractory B-cell cancers. However, the therapy is associated with significant toxicities and impaired hematopoietic recovery among certain patients.

Juluri and colleagues sought to identify factors associated with hematopoietic recovery after CD19 CAR T-cell therapy among 125 patients with relapsed or refractory acute lymphoblastic leukemia (n = 44; median age, 40 years; 54.5% men), non-Hodgkin lymphoma (n = 44; median age, 57 years; 65.9% men) and chronic lymphocytic leukemia (n = 37; median age, 61 years; 64.9% men).

The researchers defined criteria for neutropenia, thrombocytopenia and recovery according to Center for International Blood and Marrow Transplant Research reporting guidelines. For competing risk analysis, they defined an event as absolute neutrophil count (ANC) or platelet recovery. Death, new cytotoxic therapy, and relapse with marrow involvement in the absence of ANC or platelet recovery were considered competing events.

Multivariable analyses included patient, disease and CAR T-cell therapy-related variables.

Results showed that 91% of all patients (ALL, 86%; CLL, 92%; NHL, 95%) experienced ANC recovery and 86% (ALL, 86%; CLL, 86%; NHL, 84%) experienced platelet recovery after treatment.

Median time to ANC recovery was 9 days, with a probability of 80% (95% CI, 73-87) at day 28, 86% (95% CI, 80-92) at day 60 and 89% (95% CI, 83-94) at day 90.

The probability of platelet recovery was 55% (95% CI, 46-64) on the day of CAR-T infusion, 74% (95% CI, 67-82) on day 28, 83% (95% CI, 76-90) on day 60 and 84% (95% CI, 77-90) on day 90.

Researchers always observed a competing event among patients without ANC or platelet recovery.

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Multivariable analysis showed associations between faster ANC recovery and higher pre-lymphodepletion platelet count, as well as higher peak CD8-positive CAR T cells in blood.

A diagnosis of ALL appeared associated with slower ANC recovery compared with CLL and NHL (CLL vs. ALL, HR = 1.6; P = .02; NHL vs. ALL, HR = 2.07; P = .007).

Higher grade of cytokine release syndrome appeared associated with slower platelet recovery (HR per grade increase = 0.67; P < .001), whereas higher pre-lymphodepletion platelet count (HR per 25 x 10/L increase = 1.08; P = .001) and higher peak CD8-positive CAR T cells in blood (HR per log cells/µL increase = 1.41; P < .001) appeared associated with faster platelet recovery.

“The other aspect is a more careful measurement of cytokines or detecting [cytokine release syndrome] earlier before it gets to a higher grade,” Juluri said. “These patients are generally treated in the intensive care unit and are quite sick, so if we can detect it and treat it earlier ... it will really help them in their recovery.” – by John DeRosier

Reference:

Juluri KR, et al. Abstract 479. Presented at: TCT | Transplantation & Cellular Therapy Meetings; Feb. 19-23, 2020; Orlando.

Disclosures: Juluri reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.